Alzheimer's blood-based biomarkers, incident dementia, and interactions with age, APOE status, and hormone therapy

Cognitive impairment among older adults is often due to multiple pathologies and heterogenous risk factors. We assessed whether Alzheimer's blood-based biomarkers (BBMs) were associated with incident mild cognitive impairment (MCI)/probable dementia, and whether associations were modified by age, apolipoprotein E (APOE), and hormone therapy (HT).

Analyses included 2467 Women's Health Initiative Memory Study women (≥65 years of age) randomized between 1995 and 1998 to 3-5-years of HT or placebo. Cox regression (mean 18-year follow-up) assessed associations between the z-scored BBMs and MCI/dementia.

Lower baseline amyloid beta (Aβ)42/40 ratio and higher phosphorylated tau 181 (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were associated with an increased risk of MCI and dementia; GFAP was most strongly associated. The p-tau181 and NfL associations were stronger among APOE ε4 carriers; BBMs varied non-linearly by age. The associations of BBMs with the cognitive outcomes also varied inconsistently between HT groups.

BBMs for AD and related dementias (ADRD) are associated with incident MCI/dementia in older women. Interactions between the BBMs and HT were inconsistent and require further investigation.